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Mr. E.A. is a 40-year-old black male who presented to his Primary Care Provider for a diabetes follow up on October 14th, 2019. The patient complains of a general constant headache that has lasted the past week, with no relieving factors. He also reports an unusual increase in fatigue and general muscle ache without any change in his daily routine. Patient also reports occasional numbness and tingling of face and arms. He is concerned that these symptoms could potentially be a result of his new diabetes medication that he began roughly a week ago. Patient states that he has not had any caffeine or smoked tobacco in the last thirty minutes. During assessment vital signs read BP 165/87, Temp 97.5 , RR 16, O 98%, and HR 86. E.A states he has not lost or gained any weight. After 10 mins, the vital signs were retaken BP 170/90, Temp 97.8, RR 15, O 99% and HR 82. Hg A1c 7.8%, three months prior Hg A1c was 8.0%.  Glucose  180 mg/dL (fasting).  FAST test done; negative for stroke. CT test, Chem 7 and CBC have been ordered.

Past medical history

Diagnosed with diabetes (type 2) at 32 years old

Overweight, BMI of 31

Had a cholecystomy at 38 years old

Diagnosed with dyslipidemia at 32 years old

Past family history

Mother alive, diagnosed diabetic at 42 years old 

Father alive with Hypertension diagnosed at 55 years old

Brother alive and well at 45 years old

Sister alive and obese at 34 years old 

Pertinent social history

Social drinker on occasion

Smokes a pack of cigarettes per day

Works full time as an IT technician and is in graduate school

Hypertension A Case Study

Jul 21, 2014

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Hypertension A Case Study. Jennifer Kitchen July 19, 2013. Vicki, a patient just diagnosed with Hypertension (HTN) What is Hypertension? Appropriate T reatment Prognosis (including therapies, medications, etc.) Patient Teaching Potential B arriers to Therapy. O verview. 42 years old

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HypertensionA Case Study Jennifer Kitchen July 19, 2013

Vicki, a patient just diagnosed with Hypertension (HTN) • What is Hypertension? • Appropriate Treatment Prognosis (including therapies, medications, etc.) • Patient Teaching • Potential Barriers to Therapy Overview

42 years old • African American • Married to her high school sweetheart, Robert, for 20 yrs. • Self-employed, successful insurance agent • Busy lifestyle, travels often and eats at fast food restaurants for most meals • Blood pressure, 145 over 94 Vicki

Hypertension (HTN) is… • High Blood Pressure (BP) • A major cause of strokes and heart attacks • 1 in 4 adults have high BP • An estimated 5-10 million people have HTN but are unaware of it • HTN contributes Directly or Indirectly to almost 800,000 deaths a year • (Moser, 2012) What is Hypertension?

Normal BP is about 120/80 • Systolic pressure- pumping pressure • Diastolic pressure- resting pressure • (ACP, 2004). Normal Blood PressureWhat is Hypertension?

Table 1: Stages of hypertension Stage SystolicDiastolic Optimal <120 <80 Normal 120–12980–84 High-normal 130–139 85–89 HTN stage 1 140–159 90–99 HTN stage 2 160–179 100–109 HTN stage 3 >180 >110 Systolic and diastolic pressures given in mm Hg. (Foex, 2004) Stages of Hypertension What is Hypertension?

HTN is not curable • Can be controlled with… • Medication (drug therapy) • Diuretics, Beta-adrenergic blockers, Vasodilators, Calcium channel blockers, Angiotension-converting enzyme (ACE) inhibitors, and Angiotension receptor blockers (ARBs) • Lifestyle changes • Limit sodium intake, Reduce and maintain a healthy weight, Manage a healthy diet, Exercise, Reduce stress, and Quit smoking • (Frazier and Drzymkowski, 2009) Treatment Prognosis

Cause of HTN is Unknown, but many factors may contribute to HTN… • Age, Smoking, Heredity, Obesity, Sedentary lifestyle, Poor diet and nutrition, and Hyperactive (type A) personality • Stress is considered a Major Factor! • (Frazier and Drzymkowski, 2009) Patient Teaching

Living with HTN… • Remember high BP cannot be Cured, only Controlled • Drug therapy is important in helping control HTN • Lifestyle changes are also important • BP must be monitored regularly • (Frazier and Drzymkowski, 2009) Patient Teaching

Making lifestyle changes • “Bad habits are hard to change.” • Staying on medication • “If I can’t feel it, it must not be there.” • Monitoring BP • “My blood pressure is always higher when I go to the doctor’s office.” Potential Barriers

Sometimes all we need is to take a break on the busy tracks of life.

American College of Physicians (ACP), (2004). ACP Special Report: Living With Hypertension. Retrieved from http://www.acponline.org/patients_families/pdfs/health/hypertension_report.pdf Foex, P. and Sear, J.W., (2004). Hypertension: pathophysiology and treatment. Continuing Education in Anesthesia, Critical Care & Pain; 4:3. DOI 10.1093. Retrieved from http://ceaccp.oxfordjournals.org/content/4/3/71.full.pdf+html. Moser, M. (2012). High Blood Pressure: lower it and live longer. Hypertension Education Foundation (HEF). Retrieved from http://www.hypertensionfoundation.org/PDinfo/HBP(HEF)120611.pdf Frazier, M. S. and Dryzmkowski, J. W. (2009). Essentials of Human Diseases and Conditions (4th Ed.). St. Louis, MO: Saunders Elsevier Inc. References

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Clinical pearls, case study: treating hypertension in patients with diabetes.

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Evan M. Benjamin; Case Study: Treating Hypertension in Patients With Diabetes. Clin Diabetes 1 July 2004; 22 (3): 137–138. https://doi.org/10.2337/diaclin.22.3.137

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L.N. is a 49-year-old white woman with a history of type 2 diabetes,obesity, hypertension, and migraine headaches. The patient was diagnosed with type 2 diabetes 9 years ago when she presented with mild polyuria and polydipsia. L.N. is 5′4″ and has always been on the large side,with her weight fluctuating between 165 and 185 lb.

Initial treatment for her diabetes consisted of an oral sulfonylurea with the rapid addition of metformin. Her diabetes has been under fair control with a most recent hemoglobin A 1c of 7.4%.

Hypertension was diagnosed 5 years ago when blood pressure (BP) measured in the office was noted to be consistently elevated in the range of 160/90 mmHg on three occasions. L.N. was initially treated with lisinopril, starting at 10 mg daily and increasing to 20 mg daily, yet her BP control has fluctuated.

One year ago, microalbuminuria was detected on an annual urine screen, with 1,943 mg/dl of microalbumin identified on a spot urine sample. L.N. comes into the office today for her usual follow-up visit for diabetes. Physical examination reveals an obese woman with a BP of 154/86 mmHg and a pulse of 78 bpm.

What are the effects of controlling BP in people with diabetes?

What is the target BP for patients with diabetes and hypertension?

Which antihypertensive agents are recommended for patients with diabetes?

Diabetes mellitus is a major risk factor for cardiovascular disease (CVD). Approximately two-thirds of people with diabetes die from complications of CVD. Nearly half of middle-aged people with diabetes have evidence of coronary artery disease (CAD), compared with only one-fourth of people without diabetes in similar populations.

Patients with diabetes are prone to a number of cardiovascular risk factors beyond hyperglycemia. These risk factors, including hypertension,dyslipidemia, and a sedentary lifestyle, are particularly prevalent among patients with diabetes. To reduce the mortality and morbidity from CVD among patients with diabetes, aggressive treatment of glycemic control as well as other cardiovascular risk factors must be initiated.

Studies that have compared antihypertensive treatment in patients with diabetes versus placebo have shown reduced cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS), which followed patients with diabetes for an average of 8.5 years, found that patients with tight BP control (< 150/< 85 mmHg) versus less tight control (< 180/< 105 mmHg) had lower rates of myocardial infarction (MI), stroke, and peripheral vascular events. In the UKPDS, each 10-mmHg decrease in mean systolic BP was associated with a 12% reduction in risk for any complication related to diabetes, a 15% reduction for death related to diabetes, and an 11% reduction for MI. Another trial followed patients for 2 years and compared calcium-channel blockers and angiotensin-converting enzyme (ACE) inhibitors,with or without hydrochlorothiazide against placebo and found a significant reduction in acute MI, congestive heart failure, and sudden cardiac death in the intervention group compared to placebo.

The Hypertension Optimal Treatment (HOT) trial has shown that patients assigned to lower BP targets have improved outcomes. In the HOT trial,patients who achieved a diastolic BP of < 80 mmHg benefited the most in terms of reduction of cardiovascular events. Other epidemiological studies have shown that BPs > 120/70 mmHg are associated with increased cardiovascular morbidity and mortality in people with diabetes. The American Diabetes Association has recommended a target BP goal of < 130/80 mmHg. Studies have shown that there is no lower threshold value for BP and that the risk of morbidity and mortality will continue to decrease well into the normal range.

Many classes of drugs have been used in numerous trials to treat patients with hypertension. All classes of drugs have been shown to be superior to placebo in terms of reducing morbidity and mortality. Often, numerous agents(three or more) are needed to achieve specific target levels of BP. Use of almost any drug therapy to reduce hypertension in patients with diabetes has been shown to be effective in decreasing cardiovascular risk. Keeping in mind that numerous agents are often required to achieve the target level of BP control, recommending specific agents becomes a not-so-simple task. The literature continues to evolve, and individual patient conditions and preferences also must come into play.

While lowering BP by any means will help to reduce cardiovascular morbidity, there is evidence that may help guide the selection of an antihypertensive regimen. The UKPDS showed no significant differences in outcomes for treatment for hypertension using an ACE inhibitor or aβ-blocker. In addition, both ACE inhibitors and angiotensin II receptor blockers (ARBs) have been shown to slow the development and progression of diabetic nephropathy. In the Heart Outcomes Prevention Evaluation (HOPE)trial, ACE inhibitors were found to have a favorable effect in reducing cardiovascular morbidity and mortality, whereas recent trials have shown a renal protective benefit from both ACE inhibitors and ARBs. ACE inhibitors andβ-blockers seem to be better than dihydropyridine calcium-channel blockers to reduce MI and heart failure. However, trials using dihydropyridine calcium-channel blockers in combination with ACE inhibitors andβ-blockers do not appear to show any increased morbidity or mortality in CVD, as has been implicated in the past for dihydropyridine calcium-channel blockers alone. Recently, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in high-risk hypertensive patients,including those with diabetes, demonstrated that chlorthalidone, a thiazide-type diuretic, was superior to an ACE inhibitor, lisinopril, in preventing one or more forms of CVD.

L.N. is a typical patient with obesity, diabetes, and hypertension. Her BP control can be improved. To achieve the target BP goal of < 130/80 mmHg, it may be necessary to maximize the dose of the ACE inhibitor and to add a second and perhaps even a third agent.

Diuretics have been shown to have synergistic effects with ACE inhibitors,and one could be added. Because L.N. has migraine headaches as well as diabetic nephropathy, it may be necessary to individualize her treatment. Adding a β-blocker to the ACE inhibitor will certainly help lower her BP and is associated with good evidence to reduce cardiovascular morbidity. Theβ-blocker may also help to reduce the burden caused by her migraine headaches. Because of the presence of microalbuminuria, the combination of ARBs and ACE inhibitors could also be considered to help reduce BP as well as retard the progression of diabetic nephropathy. Overall, more aggressive treatment to control L.N.'s hypertension will be necessary. Information obtained from recent trials and emerging new pharmacological agents now make it easier to achieve BP control targets.

Hypertension is a risk factor for cardiovascular complications of diabetes.

Clinical trials demonstrate that drug therapy versus placebo will reduce cardiovascular events when treating patients with hypertension and diabetes.

A target BP goal of < 130/80 mmHg is recommended.

Pharmacological therapy needs to be individualized to fit patients'needs.

ACE inhibitors, ARBs, diuretics, and β-blockers have all been documented to be effective pharmacological treatment.

Combinations of drugs are often necessary to achieve target levels of BP control.

ACE inhibitors and ARBs are agents best suited to retard progression of nephropathy.

Evan M. Benjamin, MD, FACP, is an assistant professor of medicine and Vice President of Healthcare Quality at Baystate Medical Center in Springfield, Mass.

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A 21-Year-Old Pregnant Woman with Hypertension and Proteinuria

• Andrea Luk,

* To whom correspondence should be addressed. E-mail: [email protected]

• Ching Wan Lam,
• Wing Hung Tam,
• Anthony W. I Lo,
• Enders K. W Ng,
• Alice P. S Kong,
• Wing Yee So,
• Chun Chung Chow
• Andrea Luk, 
• Ronald C. W Ma, 
• Ching Wan Lam, 
• Wing Hung Tam, 
• Anthony W. I Lo, 
• Enders K. W Ng, 
• Alice P. S Kong, 
• Wing Yee So, 

Published: February 24, 2009

• https://doi.org/10.1371/journal.pmed.1000037
• Reader Comments

Citation: Luk A, Ma RCW, Lam CW, Tam WH, Lo AWI, Ng EKW, et al. (2009) A 21-Year-Old Pregnant Woman with Hypertension and Proteinuria. PLoS Med 6(2): e1000037. https://doi.org/10.1371/journal.pmed.1000037

Copyright: © 2009 Luk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The authors received no specific funding for this article.

Competing interests: RCWM is Section Editor of the Learning Forum. The remaining authors have declared that no competing interests exist.

Abbreviations: CT, computer tomography; I, iodine; MIBG, metaiodobenzylguanidine; MRI, magnetic resonance imaging; SDH, succinate dehydrogenase; SDHD, succinate dehydrogenase subunit D

Provenance: Commissioned; externally peer reviewed

Description of Case

A 21-year-old pregnant woman, gravida 2 para 1, presented with hypertension and proteinuria at 20 weeks of gestation. She had a history of pre-eclampsia in her first pregnancy one year ago. During that pregnancy, at 39 weeks of gestation, she developed high blood pressure, proteinuria, and deranged liver function. She eventually delivered by emergency caesarean section following failed induction of labour. Blood pressure returned to normal post-partum and she received no further medical follow-up. Family history was remarkable for her mother's diagnosis of hypertension in her fourth decade. Her father and five siblings, including a twin sister, were healthy. She did not smoke nor drink any alcohol. She was not taking any regular medications, health products, or herbs.

At 20 weeks of gestation, blood pressure was found to be elevated at 145/100 mmHg during a routine antenatal clinic visit. Aside from a mild headache, she reported no other symptoms. On physical examination, she was tachycardic with heart rate 100 beats per minute. Body mass index was 16.9 kg/m 2 and she had no cushingoid features. Heart sounds were normal, and there were no signs suggestive of congestive heart failure. Radial-femoral pulses were congruent, and there were no audible renal bruits.

Baseline laboratory investigations showed normal renal and liver function with normal serum urate concentration. Random glucose was 3.8 mmol/l. Complete blood count revealed microcytic anaemia with haemoglobin level 8.3 g/dl (normal range 11.5–14.3 g/dl) and a slightly raised platelet count of 446 × 10 9 /l (normal range 140–380 × 10 9 /l). Iron-deficient state was subsequently confirmed. Quantitation of urine protein indicated mild proteinuria with protein:creatinine ratio of 40.6 mg/mmol (normal range <30 mg/mmol in pregnancy).

What Were Our Differential Diagnoses?

An important cause of hypertension that occurs during pregnancy is pre-eclampsia. It is a condition unique to the gravid state and is characterised by the onset of raised blood pressure and proteinuria in late pregnancy, at or after 20 weeks of gestation [ 1 ]. Pre-eclampsia may be associated with hyperuricaemia, deranged liver function, and signs of neurologic irritability such as headaches, hyper-reflexia, and seizures. In our patient, hypertension developed at a relatively early stage of pregnancy than is customarily observed in pre-eclampsia. Although she had proteinuria, it should be remembered that this could also reflect underlying renal damage due to chronic untreated hypertension. Additionally, her electrocardiogram showed left ventricular hypertrophy, which was another indicator of chronicity.

While pre-eclampsia might still be a potential cause of hypertension in our case, the possibility of pre-existing hypertension needed to be considered. Box 1 shows the differential diagnoses of chronic hypertension, including essential hypertension, primary hyperaldosteronism related to Conn's adenoma or bilateral adrenal hyperplasia, Cushing's syndrome, phaeochromocytoma, renal artery stenosis, glomerulopathy, and coarctation of the aorta.

Box 1: Causes of Hypertension in Pregnancy

• Pre-eclampsia
• Essential hypertension
• Renal artery stenosis
• Glomerulopathy
• Renal parenchyma disease
• Primary hyperaldosteronism (Conn's adenoma or bilateral adrenal hyperplasia)
• Cushing's syndrome
• Phaeochromocytoma
• Coarctation of aorta
• Obstructive sleep apnoea

Renal causes of hypertension were excluded based on normal serum creatinine and a bland urinalysis. Serology for anti-nuclear antibodies was negative. Doppler ultrasonography of renal arteries showed normal flow and no evidence of stenosis. Cushing's syndrome was unlikely as she had no clinical features indicative of hypercortisolism, such as moon face, buffalo hump, violaceous striae, thin skin, proximal muscle weakness, or hyperglycaemia. Plasma potassium concentration was normal, although normokalaemia does not rule out primary hyperaldosteronism. Progesterone has anti-mineralocorticoid effects, and increased placental production of progesterone may mask hypokalaemia. Besides, measurements of renin activity and aldosterone concentration are difficult to interpret as the renin-angiotensin-aldosterone axis is typically stimulated in pregnancy. Phaeochromocytoma is a rare cause of hypertension in pregnancy that, if unrecognised, is associated with significant maternal and foetal morbidity and mortality. The diagnosis can be established by measuring levels of catecholamines (noradrenaline and adrenaline) and/or their metabolites (normetanephrine and metanephrine) in plasma or urine.

What Was the Diagnosis?

Catecholamine levels in 24-hour urine collections were found to be markedly raised. Urinary noradrenaline excretion was markedly elevated at 5,659 nmol, 8,225 nmol, and 9,601 nmol/day in repeated collections at 21 weeks of gestation (normal range 63–416 nmol/day). Urinary adrenaline excretion was normal. Pregnancy may induce mild elevation of catecholamine levels, but the marked elevation of urinary catecholamine observed was diagnostic of phaeochromocytoma. Conditions that are associated with false positive results, such as acute myocardial infarction, congestive heart failure, acute cerebrovascular event, withdrawal from alcohol, withdrawal from clonidine, and cocaine abuse, were not present in our patient.

The working diagnosis was therefore phaeochromocytoma complicating pregnancy. Magnetic resonance imaging (MRI) of neck to pelvis, without gadolinium enhancement, was performed at 24 weeks of gestation. It showed a 4.2 cm solid lesion in the mid-abdominal aorto-caval region, while both adrenals were unremarkable. There were no ectopic lesions seen in the rest of the examined areas. Based on existing investigation findings, it was concluded that she had extra-adrenal paraganglioma resulting in hypertension.

What Was the Next Step in Management?

At 22 weeks of gestation, the patient was started on phenoxybenzamine titrated to a dose of 30 mg in the morning and 10 mg in the evening. Propranolol was added several days after the commencement of phenoxybenzamine. Apart from mild postural dizziness, the medical therapy was well tolerated during the remainder of the pregnancy. In the third trimester, systolic and diastolic blood pressures were maintained to below 90 mmHg and 60 mmHg, respectively. During this period, she developed mild elevation of alkaline phosphatase ranging from 91 to 188 IU/l (reference 35–85 IU/l). However, liver transaminases were normal and the patient had no seizures. Repeated urinalysis showed resolution of proteinuria. At 38 weeks of gestation, the patient proceeded to elective caesarean section because of previous caesarean section, and a live female baby weighing 3.14 kg was delivered. The delivery was uncomplicated and blood pressure remained stable.

Following the delivery, computer tomography (CT) scan of neck, abdomen, and pelvis was performed as part of pre-operative planning to better delineate the relationship of the tumour to neighbouring structures. In addition to the previously identified extra-adrenal paraganglioma in the abdomen ( Figure 1 ), the CT revealed a 9 mm hypervascular nodule at the left carotid bifurcation, suggestive of a carotid body tumour ( Figure 2 ). The patient subsequently underwent an iodine (I) 131 metaiodobenzylguanidine (MIBG) scan, which demonstrated marked MIBG-avidity of the paraganglioma in the mid-abdomen. The reported left carotid body tumour, however, did not demonstrate any significant uptake. This could indicate either that the MIBG scan had poor sensitivity in detecting a small tumour, or that the carotid body tumour was not functional.

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https://doi.org/10.1371/journal.pmed.1000037.g001

https://doi.org/10.1371/journal.pmed.1000037.g002

In June 2008, four months after the delivery, the patient had a laparotomy with removal of the abdominal paraganglioma. The operation was uncomplicated. There was no wide fluctuation of blood pressures intra- and postoperatively. Phenoxybenzamine and propranolol were stopped after the operation. Histology of the excised tumour was consistent with paraganglioma with cells staining positive for chromogranin ( Figures 3 and 4 ) and synaptophysin. Adrenal tissues were notably absent.

The tumour is a well-circumscribed fleshy yellowish mass with maximal dimension of 5.5 cm.

https://doi.org/10.1371/journal.pmed.1000037.g003

The tumour cells are polygonal with bland nuclei. The cells are arranged in nests and are immunoreactive to chromogranin (shown here) and synaptophysin.

https://doi.org/10.1371/journal.pmed.1000037.g004

The patient was counselled for genetic testing for hereditary phaeochromocytoma/paraganglioma. She was found to be heterozygous for c.449_453dup mutation of the succinate dehydrogenase subunit D (SDHD) gene ( Figure 5 ). This mutation is a novel frameshift mutation, and leads to SDHD deficiency (GenBank accession number: 1162563). At the latest clinic visit in August 2008, she was asymptomatic and normotensive. Measurements of catecholamine in 24-hour urine collections had normalised. Resection of the left carotid body tumour was planned for a later date. She was to be followed up indefinitely to monitor for recurrences. She was also advised to contact family members for genetic testing. Our patient gave written consent for this case to be published.

https://doi.org/10.1371/journal.pmed.1000037.g005

Phaeochromocytoma in Pregnancy

Hypertension during pregnancy is a frequently encountered obstetric complication that occurs in 6%–8% of pregnancies [ 2 ]. Phaeochromocytoma presenting for the first time in pregnancy is rare, and only several hundred cases have been reported in the English literature. In a recent review of 41 cases that presented during 1988 to 1997, maternal mortality was 4% while the rate of foetal loss was 11% [ 3 ]. Antenatal diagnosis was associated with substantial reduction in maternal mortality but had little impact on foetal mortality. Further, chronic hypertension, regardless of aetiology, increases the risk of pre-eclampsia by 10-fold [ 1 ].

Classically, patients with phaeochromocytoma present with spells of palpitation, headaches, and diaphoresis [ 4 ]. Hypertension may be sustained or sporadic, and is associated with orthostatic blood pressure drop because of hypovolaemia and impaired vasoconstricting response to posture change. During pregnancy, catecholamine surge may be triggered by pressure from the enlarging uterus and foetal movements. In the majority of cases, catecholamine-secreting tumours develop in the adrenal medulla and are termed phaeochromocytoma. Ten percent of tumours arise from extra-adrenal chromaffin tissues located in the abdomen, pelvis, or thorax to form paraganglioma that may or may not be biochemically active. The malignant potential of phaeochromocytoma or paraganglioma cannot be determined from histology and is inferred by finding tumours in areas of the body not known to contain chromaffin tissues. The risk of malignancy is higher in extra-adrenal tumours and in tumours that secrete dopamine.

Making the Correct Diagnosis

The diagnosis of phaeochromocytoma requires a combination of biochemical and anatomical confirmation. Catecholamines and their metabolites, metanephrines, can be easily measured in urine or plasma samples. Day collection of urinary fractionated metanephrine is considered the most sensitive in detecting phaeochromocytoma [ 5 ]. In contrast to sporadic release of catecholamine, secretion of metanephrine is continuous and is less subjective to momentary stress. Localisation of tumour can be accomplished by either CT or MRI of the abdomen [ 6 ]. Sensitivities are comparable, although MRI is preferable in pregnancy because of minimal radiation exposure. Once a tumour is identified, nuclear medicine imaging should be performed to determine its activity, as well as to search for extra-adrenal diseases. I 131 or I 123 MIBG scan is the imaging modality of choice. Metaiodobenzylguanidine structurally resembles noradrenaline and is concentrated in chromaffin cells of phaeochromocytoma or paraganglioma that express noradrenaline transporters. Radionucleotide imaging is contraindicated in pregnancy and should be deferred until after the delivery.

Treatment Approach

Upon confirming the diagnosis, medical therapy should be initiated promptly to block the cardiovascular effects of catecholamine release. Phenoxybenzamine is a long-acting non-selective alpha-blocker commonly used in phaeochromocytoma to control blood pressure and prevent cardiovascular complications [ 7 ]. The main side-effects of phenoxybenzamine are postural hypotension and reflex tachycardia. The latter can be circumvented by the addition of a beta-blocker. It is important to note that beta-blockers should not be used in isolation, since blockade of ß2-adrenoceptors, which have a vasodilatory effect, can cause unopposed vasoconstriction by a1-adrenoceptor stimulation and precipitate severe hypertension. There is little data on the safety of use of phenoxybenzamine in pregnancy, although its use is deemed necessary and probably life-saving in this precarious situation.

The definitive treatment of phaeochromocytoma or paraganglioma is surgical excision. The timing of surgery is critical, and the decision must take into consideration risks to the foetus, technical difficulty regarding access to the tumour in the presence of a gravid uterus, and whether the patient's symptoms can be satisfactorily controlled with medical therapy [ 8 , 9 ]. It has been suggested that surgical resection is reasonable if the diagnosis is confirmed and the tumour identified before 24 weeks of gestation. Otherwise, it may be preferable to allow the pregnancy to progress under adequate alpha- and beta-blockade until foetal maturity is reached. Unprepared delivery is associated with a high risk of phaeochromocytoma crisis, characterised by labile blood pressure, tachycardia, fever, myocardial ischaemia, congestive heart failure, and intracerebral bleeding.

Patients with phaeochromocytoma or paraganglioma should be followed up for life. The rate of recurrence is estimated to be 2%–4% at five years [ 10 ]. Assessment for recurrent disease can be accomplished by periodic blood pressure monitoring and 24-hour urine catecholamine and/or metanephrine measurements.

Genetics of Phaeochromocytoma

Approximately one quarter of patients presenting with phaeochromocytoma may carry germline mutations, even in the absence of apparent family history [ 11 ]. The common syndromes of hereditary phaeochromocytoma/paraganglioma are listed in Box 2 . These include Von Hippel-Lindau syndrome, multiple endocrine neoplasia type 2, neurofibromatosis type 1, and succinate dehydrogenase (SDH) gene mutations. Our patient has a novel frameshift mutation in the SDHD gene located at Chromosome 11q. SDH is a mitochondrial enzyme that is involved in oxidative phosphorylation. Characteristically, SDHD mutation is associated with head or neck non-functional paraganglioma, and infrequently, sympathetic paraganglioma or phaeochromocytoma [ 12 ]. Tumours associated with SDHD mutation are rarely malignant, in contrast to those arisen from mutation of the SDHB gene. Like all other syndromes of hereditary phaeochromocytoma, SDHD mutation is transmitted in an autosomal dominant fashion. However, not all carriers of the SDHD mutation develop tumours, and inheritance is further complicated by maternal imprinting in gene expression. While it may not be practical to screen for genetic alterations in all cases of phaeochromocytoma, most authorities advocate genetic screening for patients with positive family history, young age of tumour onset, co-existence with other neoplasms, bilateral phaeochromocytoma, and extra-adrenal paraganglioma. The confirmation of genetic mutation should prompt evaluation of other family members.

Box 2: Hereditary Phaeochromocytoma/Paraganglioma Syndromes

• Von Hippel-Lindau syndrome
• Multiple endocrine neoplasia type 2A and type 2B
• Neurofibromatosis type 1
• Mutation of SDHB , SDHC , SDHD
• Ataxia-telangiectasia
• Tuberous sclerosis
• Sturge-Weber syndrome

Key Learning Points

• Hypertension complicating pregnancy is a commonly encountered medical condition.
• Pre-existing chronic hypertension must be considered in patients with hypertension presenting in pregnancy, particularly if elevation of blood pressure is detected early during pregnancy or if persists post-partum.
• Secondary causes of chronic hypertension include renal artery stenosis, renal parenchyma disease, primary hyperaldosteronism, phaeochromocytoma, Cushing's syndrome, coarctation of the aorta, and obstructive sleep apnoea.
• Phaeochromocytoma presenting during pregnancy is rare but carries high rates of maternal and foetal morbidity and mortality if unrecognised.
• Successful outcomes depend on early disease identification, prompt initiation of alpha- and beta-blockers, carefully planned delivery, and timely resection of the tumour.

Phaeochromocytoma complicating pregnancy is uncommon. Nonetheless, in view of the potential for catastrophic consequences if unrecognised, a high index of suspicion and careful evaluation for secondary causes of hypertension is of utmost importance. Blood pressure should be monitored in the post-partum period and persistence of hypertension must be thoroughly investigated.

Author Contributions

All authors participated in the management of the patient or writing of the article. AL and RCWM wrote the article, with contributions from all the authors.

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Case Studies: BP Evaluation and Treatment in Patients with Prediabetes or Diabetes

—the new acc/aha blood pressure guidelines call for a more aggressive diagnostic and treatment approach in most situations..

By Kevin O. Hwang, MD, MPH, Associate Professor, McGovern Medical School, Houston, TX

The following case studies illustrate how the new ACC/AHA guideline specifies a shift in the definition of BP categories and treatment targets.

A 59-year-old man with type 2 diabetes presents with concerns about high blood pressure (BP). At a recent visit to his dentist he was told his BP was high. He was reclining in the dentist’s chair when his BP was taken, but he doesn’t remember the exact reading. He has no symptoms. He has never taken medications for high BP. He takes metformin for type 2 diabetes.

His BP is measured once at 146/95 mm Hg in the left arm while sitting. Physical exam is unremarkable except for obesity. EKG is unremarkable.

BP Measurement

Controlling BP in patients with diabetes reduces the risk of cardiovascular events, but the available data are not sufficient to classify this patient with respect to BP status. The reading taken while reclining in the dentist’s chair was likely inaccurate. A single reading in the medical clinic, even with correct technique, is not adequate for clinical decision-making because individual BP measurements vary in unpredictable or random ways.

The accuracy of BP measurement is affected by patient preparation and positioning, technique, and timing. Before the first reading, the patient should avoid smoking, caffeine, and exercise for at least 30 minutes and should sit quietly in a chair for at least 5 minutes with back supported and feet flat on the floor. An appropriately sized cuff should be placed on the bare upper arm and with the arm supported at heart level. For the first encounter, BP should be recorded in both arms. The arm with the higher reading should be used for subsequent measurements.

It is recommended that one use an average of 2 to 3 readings, separated by 1 to 2 minutes, obtained on 2 to 3 separate visits. Some of those readings should be performed outside of the clinical setting, either with home BP self-monitoring or 24-hour ambulatory BP monitoring, especially when confirming the diagnosis of sustained hypertension. Note that a clinic BP of 140/90 corresponds to home BP values of 135/85. Multiple BP readings in the clinic and at home allow for classification into one of the following categories.

The BP is measured in the office with the correct technique and timing referenced above. The patient is educated on how on to measure BP at home with a validated monitor. He should take at least 2 readings 1 minute apart in the morning and in the evening before supper (4 readings per day). The optimal schedule is to measure BP every day for a week before the next clinic visit, which is set for a month from now. Obtaining multiple clinic and home BP readings on multiple days will support a well-informed assessment of the patient’s BP status and subsequent treatment decisions.

A 62 year old African-American woman with prediabetes presents for her annual physical. She has no complaints. The average of 2 BP readings in her right arm is BP 143/88. Her physical exam is unremarkable except for obesity. She has no history of myocardial infarction, stroke, kidney disease, or heart failure. After the visit, she measures her BP at home and returns 1 month later. The average BP from multiple clinic and home readings is 138/86.

Her total cholesterol is 260 mg/dL, HDL 42 mg/dL, and LDL 165 mg/dL. She does not smoke.

Stage 1 Hypertension

Under the 2017 ACC/AHA guideline, she has stage 1 hypertension (HTN). This guideline uses a uniform BP definition for HTN without regard to patient age or comorbid illnesses, such as diabetes or chronic kidney disease.

In patients with stage 1 HTN and no known atherosclerotic cardiovascular disease (ASCVD) , the new guideline recommends treating with BP-lowering medications if the 10-year risk for ASCVD risk is 10% or greater. With input such as her age, gender, race, lipid profile, and other risk factors, the ACC/AHA Pooled Cohort Equations tool estimates her 10-year risk to be approximately 10.5%.

With stage 1 HTN and 10-year ASCVD risk of 10% or higher, she would benefit from a BP-lowering medication. Thiazide diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and calcium channel blockers are first-line agents for HTN because they reduce the risk of clinical events. In African-Americans, thiazide diuretics and calcium channel blockers are more effective for lowering BP and preventing cardiovascular events compared to ACE inhibitors or ARBs.

Patient-specific factors, such as age, comorbidities, concurrent medications, drug adherence, and out-of-pocket costs should be considered. Shared decision making should drive the ultimate choice of antihypertensive medication(s).

Nonpharmacologic strategies for prediabetes and HTN include dietary changes, physical activity, and weight loss. If clinically appropriate, she should also avoid agents which could elevate BP, such as NSAIDs, oral steroids, stimulants, and decongestants.

A goal BP of 130/80 is recommended. After starting the new BP medication, she should monitor BP at home and return to the clinic in 1 month. If the BP goal is not met at that time despite adherence to treatment, consideration should be given to intensifying treatment by increasing the dose of the first medication or adding a second agent.

A 63 year old man with type 2 diabetes has an average BP of 151/92 over the span of several weeks of measuring at home and in the clinic. He also has albuminuria.

Stage 2 Hypertension:

The BP treatment goal patients with diabetes and HTN is less than 130/80. While some patients can be effectively treated with a single agent, serious consideration should be given to starting with 2 drugs of different classes, especially if BP is more than 20/10 mm Hg above their BP target. Giving both medications as a fixed-dose combination may improve adherence.

In this man with diabetes and HTN, any of the first-line classes of antihypertensive agents (diuretics, ACE inhibitors, ARBs, and CCBs) would be reasonable choices. Given the presence of albuminuria, an ACE inhibitor or ARB would be beneficial for slowing progression of kidney disease. However, an ACE inhibitor and ARB should not be used simultaneously due to an increase in cardiovascular and renal risk observed in clinical trials.

He is started on a fixed-dose combination of an ACE-inhibitor and thiazide diuretic. He purchases a validated BP monitor which can transmit BP readings to his provider’s electronic health records system. Direct transmission of BP data to the provider has been shown to help patients achieve greater reductions in BP compared to self-monitoring without transmission of data. One month follow-up is recommended to determine if the treatment goal has been met.

Published: April 30, 2018

• 2. Final Recommendation Statement: High Blood Pressure in Adults: Screening. U.S. Preventive Services Task Force. September 2017.

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Factors Associated with Neonatal Arterial Hypertension: Case and Control Study

• Department of Psychiatry and Mental Health
• Department of Clinical Epidemiology and Biostatistics
• Universidad Javeriana
• San Ignacio University Hospital
• Subred Integrada de Servicios de Salud Sur

Research output : Contribution to journal › Article › peer-review

Background. Neonatal high blood pressure has been diagnosed more frequently in recent years, and its impact extends to adulthood. However, the knowledge gaps on associated factors, diagnosis, and treatment are challenging for medical personnel. The incidence of this condition varies depending on neonatal conditions. Patients in the Newborn Unit are at increased risk of developing high blood pressure. The persistence of this condition beyond the neonatal stage increases the risk of cardiovascular disease and chronic kidney disease in childhood and adulthood. Methodology. A case-control study was carried out. It included hospitalized patients with neonatal hypertension as cases. Three controls were randomly selected for each case and matched by gestational age. The variables were analyzed based on their nature. Multivariate analysis was performed using a multivariate conditional regression model to identify variables associated with the outcome. Finally, the model was adjusted for possible confounders. Results. 37 cases were obtained and matched with 111 controls. In the univariate analysis, heart disease (OR 2.86; 95% CI 1.22-6.71), kidney disease (OR 7.24; 95% CI 1.92-28.28), bronchopulmonary dysplasia (OR 6.62; 95% CI 1.42-50.82) and major surgical procedures (OR 3.71; 95% CI 1.64-8.39) had an association with neonatal arterial hypertension. Only the latter maintained this finding in the multivariate analysis (adjusted OR 2.88; 95% CI 1.14-7.30). A significant association of two or more comorbidities with neonatal arterial hypertension was also found (OR 3.81; 95% CI 1.53-9.49). Conclusions. The study analyzed the factors related to high blood pressure in hospitalized neonates, finding relevant associations in the said population. The importance of meticulous neonatal care and monitoring of risk factors such as birth weight and major surgeries is highlighted.

• Blood Pressure
• Bronchopulmonary Dysplasia
• Epigenetics
• Hypertension
• Kidney Disease
• Prematurity

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• Hypertension Nursing and Health Professions 100%
• Blood Pressure Biochemistry, Genetics and Molecular Biology 100%
• Multivariate Analysis Nursing and Health Professions 33%
• Dysplasia Biochemistry, Genetics and Molecular Biology 33%
• Newborn Care Nursing and Health Professions 16%
• Major Surgery Nursing and Health Professions 16%
• Heart Disease Nursing and Health Professions 16%
• Lung Dysplasia Nursing and Health Professions 16%

T1 - Factors Associated with Neonatal Arterial Hypertension

T2 - Case and Control Study

AU - Gutiérrez-Cortés, Carolina

AU - Lince-Rivera, Catalina

AU - Bohórquez-Peñaranda, Adriana P.

AU - Castillo-Arteaga, Mariangel

AU - Mayerly Gómez, Ingrid

AU - Cárdenas-Aguilera, Juan Guillermo

N1 - Publisher Copyright: Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.

PY - 2024/4/29

Y1 - 2024/4/29

N2 - Background. Neonatal high blood pressure has been diagnosed more frequently in recent years, and its impact extends to adulthood. However, the knowledge gaps on associated factors, diagnosis, and treatment are challenging for medical personnel. The incidence of this condition varies depending on neonatal conditions. Patients in the Newborn Unit are at increased risk of developing high blood pressure. The persistence of this condition beyond the neonatal stage increases the risk of cardiovascular disease and chronic kidney disease in childhood and adulthood. Methodology. A case-control study was carried out. It included hospitalized patients with neonatal hypertension as cases. Three controls were randomly selected for each case and matched by gestational age. The variables were analyzed based on their nature. Multivariate analysis was performed using a multivariate conditional regression model to identify variables associated with the outcome. Finally, the model was adjusted for possible confounders. Results. 37 cases were obtained and matched with 111 controls. In the univariate analysis, heart disease (OR 2.86; 95% CI 1.22-6.71), kidney disease (OR 7.24; 95% CI 1.92-28.28), bronchopulmonary dysplasia (OR 6.62; 95% CI 1.42-50.82) and major surgical procedures (OR 3.71; 95% CI 1.64-8.39) had an association with neonatal arterial hypertension. Only the latter maintained this finding in the multivariate analysis (adjusted OR 2.88; 95% CI 1.14-7.30). A significant association of two or more comorbidities with neonatal arterial hypertension was also found (OR 3.81; 95% CI 1.53-9.49). Conclusions. The study analyzed the factors related to high blood pressure in hospitalized neonates, finding relevant associations in the said population. The importance of meticulous neonatal care and monitoring of risk factors such as birth weight and major surgeries is highlighted.

AB - Background. Neonatal high blood pressure has been diagnosed more frequently in recent years, and its impact extends to adulthood. However, the knowledge gaps on associated factors, diagnosis, and treatment are challenging for medical personnel. The incidence of this condition varies depending on neonatal conditions. Patients in the Newborn Unit are at increased risk of developing high blood pressure. The persistence of this condition beyond the neonatal stage increases the risk of cardiovascular disease and chronic kidney disease in childhood and adulthood. Methodology. A case-control study was carried out. It included hospitalized patients with neonatal hypertension as cases. Three controls were randomly selected for each case and matched by gestational age. The variables were analyzed based on their nature. Multivariate analysis was performed using a multivariate conditional regression model to identify variables associated with the outcome. Finally, the model was adjusted for possible confounders. Results. 37 cases were obtained and matched with 111 controls. In the univariate analysis, heart disease (OR 2.86; 95% CI 1.22-6.71), kidney disease (OR 7.24; 95% CI 1.92-28.28), bronchopulmonary dysplasia (OR 6.62; 95% CI 1.42-50.82) and major surgical procedures (OR 3.71; 95% CI 1.64-8.39) had an association with neonatal arterial hypertension. Only the latter maintained this finding in the multivariate analysis (adjusted OR 2.88; 95% CI 1.14-7.30). A significant association of two or more comorbidities with neonatal arterial hypertension was also found (OR 3.81; 95% CI 1.53-9.49). Conclusions. The study analyzed the factors related to high blood pressure in hospitalized neonates, finding relevant associations in the said population. The importance of meticulous neonatal care and monitoring of risk factors such as birth weight and major surgeries is highlighted.

KW - Blood Pressure

KW - Bronchopulmonary Dysplasia

KW - Epigenetics

KW - Hypertension

KW - Kidney Disease

KW - Neonate

KW - Prematurity

UR - http://www.scopus.com/inward/record.url?scp=85192030219&partnerID=8YFLogxK

M3 - Article

C2 - 38695229

AN - SCOPUS:85192030219

SN - 0393-5590

JO - Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia

JF - Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia